Method for improving kidney function with extracorporeal shockwaves

ABSTRACT

The present invention relates to a method for treating the kidney with extracorporeal shockwaves in a noninvasive manner and in particular, to such a method for the treatment of the nephrons about the glomerulus.

RELATED APPLICATIONS

This Application is a continuation of U.S. patent application Ser. No.15/452,568 filed Mar. 7, 2017, which is in turn a continuation of U.S.patent application Ser. No. 13/359,538 filed Jan. 27, 2012.

FIELD OF THE INVENTION

The present invention relates to a method for treating the kidney withextracorporeal shockwaves in a noninvasive manner and in particular, tosuch a method for the treatment of the nephrons about the glomerulus.

BACKGROUND OF THE INVENTION

Extracorporeal shockwave therapy (herein referred to as ‘ESWT’) isnon-surgical, non-invasive treatment of medical conditions usingacoustic shockwaves. First use of shockwave therapy in the early 1980'swas utilized to fragment kidney stones termed shockwave lithotripsy.Continued development of shockwave treatment showed the possibility ofstimulating bone formation, angiogenesis, as well as other orthopedicindications. However, medical literature suggests that lithotripsycreates hypertension and some damage to the kidney including hematuriaduring the procedure.

A shockwave is a form of acoustic energy resulting from phenomena thatcreate a sudden intense change in pressure for example an explosion orlightning. The intense changes in pressure produce strong waves ofenergy that can travel through any elastic medium such as air, water,human soft tissue, or certain solid substances such as bone.

Shockwaves are characterized by the delivery of a sequence of transientpressure disturbances characterized by an initial high peak pressurewith a fast pressure rise followed by rapid wave propagation withdiminishing amplitude over its lifecycle. Such that shockwavescharacteristically have a quick lifecycle, starting with a big highamplitude pressure peak followed by a gradual diminishing pressureamplitude having amplitude of about 10-20% of the initial pressure peak.Shockwave are further characterized in that they do not produce heatwithin the tissue.

Shockwaves are therefore characteristically different from ultrasound inthat the ultrasound waveform produces constant cyclic sinusoidalamplitude that produces heat at the tissue level. Conversely shockwavesdo not have constant amplitude over time.

Acoustic shockwaves are primarily generated by three different methods,electrohydraulic (also referred to as spark gap), electromagnetic (alsoreferred to as ‘EMSE’), and piezoelectric. Each method needs anapparatus to focus the generated shockwave so as to provide a focalpoint and/or focal zone for the treatment area. In the focal zoneshockwaves produce much higher pressure impulses as compared with thezones outside of the focal zone.

Mechanical means for focusing each of these methods is generallyrealized with an appropriate arrangement of surfaces reflecting the wavetoward the desired focal point and/or an appropriate arrangement of thegenerating devices.

Spark gap systems incorporate an electrode (spark plug), to initiate ashockwave, and ellipsoid to focus the shockwave. EMSE systems utilize anelectromagnetic coil and an opposing metal membrane. Piezoelectricsystems form acoustical waves by mounting piezoelectric crystals to aspherical surface to provide focus. Of the three systems, the spark gapsystem is generally preferred in the art for generating therapeuticshockwaves ESWT as it introduces more of the generated shockwave energyto the treatment target site.

In spark gap systems, high energy shockwaves are generated whenelectricity is applied to an electrode positioned in an ellipsoidimmersed in treated water. When the electrical charge is fired, a smallamount of water is vaporized at the tip of the electrode and a shockwaveis produced. The shockwave ricochets from the side of an ellipsoid andconverges at a focal point, which may then be transferred to the area tobe treated.

In electromagnetic systems an electrical impulse is circulated in acoil. The coil produces an electromagnetic field that expels a metallicmembrane to produce the mechanical impulse.

In piezoelectric systems ceramic material with piezoelectriccharacteristics is subjected to an electrical impulse. The electricimpulse modifies the dimension of the ceramic material to generate thedesired mechanical impulse. A focal point is attained by covering aconcave spherical surface with piezoelectric ceramics converging at thecenter of the sphere.

The method of focusing the generated shockwave has been greatlydescribed in the art for example in U.S. Pat. Nos. 5,174,280 and5,058,569, 5,033,456, EP1591070 all of which are incorporated herein byreference as if fully set forth.

Traditionally shockwaves have been used in medicine as a noninvasivemeans for treating a variety of anomalies such as kidney stones(lithotripsy), fragmentation of calcification, chronic orthopedicinflammation healing, bone healing (osteogenesis), wound healing,revascularization, angiogenesis are well known and described in medicalliterature.

U.S. Pat. No. 7,507,213 to Schultheiss, et al. discusses invasivestimulation of kidney by surgically exposing the organ for example heartor kidney prior to applying shockwave therapy.

US Patent Publication No. 2011/0257523 to Hastings et al. discusses amethod utilizing high intensity focused ultrasound (HIFU) for ablatinginnervated tissue of the kidney, for denervating renal vasculature,including disruption and termination of renal sympathetic nerveactivity, to improve cardiac and/or renal function particularly thatassociated with hypertension.

SUMMARY OF THE INVENTION

The prior art teaches methods for treating the kidney utilizing highenergy shockwave (via lithotripsy utilizing high pressure shockwaveswith energy profile of 0.6-1.1 mJ/mm²), or invasive means includingnecrosis of tissue associated with the kidney, and/or destroyingcalcification within the kidney.

The present invention overcomes the deficiencies of the background byproviding a method for treating kidney and renal structures in anoninvasive, nondestructive manner, without tissue temperature elevationutilizing low pressure shockwaves to treat and/or maintain kidneyfunction and/or improve kidney function and/or conditions associatedwith the kidney and/or renal structures and/or reduce kidney degradationand/or treat varying stages of chronic kidney disease (‘CKD’) and/orhypertension.

Within the context of this application the terms aqueous solution,aqueous medium, or aqueous environment may be used interchangeably torefer to an enclosure, opening, lumen, or space that is placed in anaqueous solution or mixture for example including but not limited towater, medicated water, ionized water, oil, gel, treated water or thelike solution or mixture in a liquid state.

Within the context of this application the term extracorporeal shockwavetherapy (‘ESWT’) refers to shockwave therapy provided with all forms ofshockwave generating device.

Within the context of this application the term shockwave treatmentdevice refers to a device comprising a controller and/or computer and ashockwave treatment applicator as is known in the art. For example, ashockwave treatment device comprises controller and/or computer thatcontrols the shockwave treatment produced by the shockwave treatmentapplicator.

Within the context of this application the term renal and/or kidneystructures refers to any of the following structures nephron,glomerulus, Bowman's capsule, tubules, medulla, renal artery, renalvein, renal pelvis, papilla, adrenal glands, adrenal cortex, adrenalmedulla, phrenic arteries, and adrenal vein, neural tissue directly orindirectly innervating the kidney and renal structures, kidney neuralsystem including renal sympathetic and renal para-sympathetic nerves,renal sympathetic nerves that lie within and immediately adjacent to thewall of the renal arteries.

Within the context of this application shockwave properties and/orparameters may be interchangeably represented in different units ofmeasure as is accepted in the art to refer to the same and/or equivalentunits of measure. For example shockwave pressure may be interchangeablyprovided in units of atmospheres (‘atm’) or Pascals (‘pa’) or megaPascals (Mpa). Shockwave frequency may be provided in relative ofabsolute units, for example including but not limited to hertz (‘Hz’)and/or shockwaves per unit time, shockwave per minute, or the like.

A preferred embodiment of the present invention provides for a methodfor noninvasive ESWT of the kidney structures and in particular theglomerulus, for maintaining and/or improving kidney function.

Optionally and preferably the method of treatment according to thepresent invention may be utilized to improve and/or increase blood flowwithin the renal and/or kidney structures, for example including but notlimited to the nephron and/or glomerulus.

Optionally and preferably the method of treatment according to thepresent invention may be utilized to remove glomerular calci.

Optionally the method of treatment according to the present inventionmay be utilized to improve hypertension in a non-destructive manner.

Optionally the method of treatment according to the present inventionmay be utilized to improve hypertension in an indirect manner forexample by improving renal blood flow, renal blood flow within theglomerulus, renal vein and/or artery and/or nerve system, neural tissuedirectly or indirectly innervating the kidney or renal structures,kidney neural system including renal sympathetic and renalpara-sympathetic nerves.

Optionally, the method of treatment of the kidney and more preferablythe glomerulus according to the present invention produces a shockwaveregimen determined based on at least one or more parameters for exampleincluding but not limited to shockwave parameters, treatment protocolparameters, anatomical parameters, or the like.

Optionally protocol parameters for example including but not limited tothe number of treatments sessions, the duration of a treatment protocol,timing of active and/or inactive treatment sessions, frequency ofsession, or the like.

Optionally the number of active treatment sessions may be provided fromabout 1 session to about 18 sessions. Optionally 12 active treatmentsmay be provided during the treatment protocol according to the presentinvention. Optionally number of active treatment session may for examplebe 1, or 2, or 3, or 4 or 5 or 6, or 7 or 8 or 9 or 10 or 11, or 12 or13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or so sessions.

Optionally the duration of the treatment protocol according to thepresent invention may be from about 1 day up to about 18 weeks or theequivalent of 1 day up to about 126 days.

Optionally treatment may be provided periodically, continuously,sequentially, intermittently, according to a schedule comprisingconsecutive sessions and/or with at least one or more intersessionrecesses. Optionally the length of the recesses may vary according tothe required treatment protocol.

Optionally, shockwave parameters may for example include but are notlimited to number of shockwaves, frequency of shockwaves and intensityof the shockwave, or the like.

Optionally shockwave intensity may be provided from about 0.02 mJ/mm² toabout 0.18 mJ/mm². Optionally and preferably shockwave intensity may beprovided from about 0.09 mJ/mm² to about 0.11 mJ/mm². Optionally andmore preferably shockwave intensity may be provided at about 0.1 mJ/mm².

Optionally Shockwave pressure utilized in embodiments of the presentinvention may for example be from about 50 atm to about 200 atm and/orfrom about 5 Mpa to about 20 Mpa.

Optionally shockwave frequency may be provided from about 60 shockwavesper minute to about 360 shockwaves per minute. Optionally and preferablya shockwave frequency may be provided from about 120 shockwaves perminute to about 240 shockwaves per minute. Optionally and mostpreferably a shockwave frequency may be provided at about 180 shockwavesper minute.

Optionally shockwave frequency may be provided from about 1 Hz to about6 Hz. Optionally and preferably a shockwave frequency may be provided atabout 2-4 Hz. Optionally and preferably a shockwave frequency may beprovided at about 2 Hz.

Optionally the number of shockwaves per treatment session may beprovided from about 100 shockwave up to about 5000 shockwaves.Optionally and most preferably about 1800 shockwaves per session may beprovided.

Optionally the number of shockwaves per treatment session may be appliedto at least one and more preferably a plurality of treatment zonesoptionally and preferably defined by kidney structures. Optionally andmore preferably a plurality of zones from about 5 up to about 15 zonesmay be treated during a treatment session. Optionally the number ofshockwaves may be distributed about a plurality of treatment zones inany manner required for the treatment, for example including evenlydistributing the number of shockwaves based on the number of zones, orby unevenly distributing the number of shockwaves per zones. Forexample, a plurality of zones from about 5 to about 15 zones may betreated with 100 shockwaves to about 500 shockwaves within a treatmentsession to provide for a treatment protocol including about 1800shockwaves to renal structures, about a plurality of zones.

Optionally the shockwave treatment according to the present inventionmay be applied to kidney structures from at least one or more optionalapproaches for example including but not limited to prone, lateral,supine, or any combination thereof, providing for appropriatenon-invasive access to the kidney structures to be treated.

A preferred embodiment of the present invention provides a method forimproving renal function by applying a noninvasive, nondestructive,extracorporeal shockwave treatment protocol to at least one kidneystructure, wherein the shockwave parameters define a low energyshockwave having a frequency of about 2 Hz and energy density of about0.02 to 0.18 mJ/mm².

Optionally the treatment according to the present invention may beapplied to a renal structure selected from the group consisting ofnephron, glomerulus, Bowman's capsule, tubules, medulla, renal artery,renal vein, renal pelvis, papilla, adrenal glands, adrenal cortex,adrenal medulla, phrenic arteries, and adrenal vein, neural tissuedirectly or indirectly innervating the kidney and renal structures,kidney neural system including renal sympathetic and renalpara-sympathetic nerves, renal sympathetic nerves that lie within andimmediately adjacent to the wall of the renal arteries.

Optionally the treatment may be directed at the glomerulus.

Optionally the treatment may be directed or otherwise adapted forapplying treatment to the renal artery.

Optionally the shockwave treatment may be dispersed about a plurality oftreatment zones, about the kidney structures. Optionally kidneystructures may for example include but is not limited to from about 5treatment zones and up to about 15 treatment zones.

Optionally the shockwave treatment may be applied to a subject from atleast one or more approaches and/or positions for example including butnot limited to lateral, prone and supine, or any combination thereof.

Optionally the treatment may be provided to provide at least one or moreselected from at least one or more of the following reduce renalinfiltration by macrophages, renal infiltration by lymphocytes,decreased expression of MCP 1 and decreased expression of CD3 mRNA,reduced Resistive Index, restored blood flow velocity in interlobularrenal arteries.

Optionally a total of 2400 shockwave are delivered to at least one ormore of the kidney structures, with a treatment energy density of about0.02 to about 0.18 mJ/mm²; at a frequency of about 2 Hz. Optionally thetreatment may be dispersed about a plurality of treatment zones and eachtreatment zone may be provided with at least 100 shockwaves.

Optionally the treatment according to optional embodiments of thepresent invention provides for at least one or more selected from thegroup consisting of: inducing regulatory factors selected from the groupconsisting of: vascular endothelial growth factor (VEGF), fibroblastgrowth factors (FGF), angiopoietins (Ang), platelet-derived growthfactor, angiogenin, angiotropin, hepatocyte growth factor, plateletendothelial cell adhesion molecule, angiostatin, endostatin,thrombospondin, CXC chemokines, Nitric oxide synthesis, NFkapaBactivation, TNF-alpha mRNA expression, increase blood flow in treatmentarea, decreases the expression of MCP 1, decrease expression of CD3mRNA, and pigment epithelium, the like or any combination thereof.

Optionally the method according to an optional embodiment of the presentinvention provides for the treatment of any one or more selected fromthe group comprising: renal dysfunction, chronic kidney disease (CKD) atany stage (1-4), Renal Insufficiency, proteinuria, diabetic nephropathyon glomerulus, vascular lesions, glomerulus calcification,tubulo-interstitial lesions, reduced blood flow in the interlobularrenal arteries, renal artery stenosis any combination thereof.

Optionally the method may provide for the reduction of the bloodpressure of the patient.

Optionally the method may provide for the reduction of intra-glomerularhypertension.

Optionally the method may be provided for maintaining kidney functionand/or improving kidney function and/or reduce kidney degradation, anycombination thereof or the like.

Optionally the method may be provided for treating chronic kidneydisease (CKD) at any stage, and/or hypertension.

Optionally the method may be provided for improving conditionsassociated with the kidney, renal structures.

Optionally the method may be provided to affect neural function orneural activity associated with the kidney structures.

Optionally wherein the affects are selected from the group consistingof: regenerating neural tissue, normalization of neural function,normalization of neural activity, modification of neural function,modification of neural activity, regulating neural activity, regulatingneural function, inhibiting neural activity, inhibiting neural function,promoting neural activity, promoting neural function, any combinationthereof.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. The materials, methods, andexamples provided herein are illustrative only and not intended to belimiting.

Implementation of the method and system of the present inventioninvolves performing or completing certain selected tasks or stepsmanually, automatically, or a combination thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin order to provide what is believed to be the most useful and readilyunderstood description of the principles and conceptual aspects of theinvention. In this regard, no attempt is made to show structural detailsof the invention in more detail than is necessary for a fundamentalunderstanding of the invention, the description taken with the drawingsmaking apparent to those skilled in the art how the several forms of theinvention may be embodied in practice.

In the Drawings:

FIG. 1 is a schematic illustrative diagram of the kidney showing thekidney structures including the adrenal gland; and optional treatmentzones comprising the nervous system innervating the kidney and the renalartery;

FIG. 2 is a schematic illustrative diagram of a Gantt chart of anoptional treatment protocol according to the present invention; and

FIG. 3 is a flowchart of an exemplary method according to the presentinvention for ESWT of kidney structures.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The principles and operation of the present invention may be betterunderstood with reference to the drawings and the accompanyingdescription.

FIG. 1 provides an illustrative schematic diagram of the kidneystructures including kidney 100, adrenal gland 110, nephron andglomerulus 102, and renal artery 50. FIG. 1 further provides a schematicillustration of a plurality of optional focal zones and/or treatmentzones 104 depicted about the kidney 100 and kidney structures associatedwith the kidney.

A preferred embodiment of the present invention provides for applyingnon-destructive and non-invasive ESWT to such kidney structures and inparticular to glomerulus 102, adrenal gland, 110 and renal artery 50,and the neural tissue associated with and/or innervating the kidneystructures. Most preferably the non-invasive ESWT applied improvesoverall kidney function. Optionally and preferably the ESWT treatment isprovided to treat and/or maintain kidney function at its current leveltherein reducing kidney degradation due to chronic diseases such ashypertension, diabetes, and/or reduced kidney function. Optionally andpreferably the ESWT of the kidney according to the present inventionfurther leads to an overall improvement in kidney function and/orconditions associated with the kidney and/or renal structures.

Optionally the ESWT treatment according to the present invention may beprovided to treat chronic kidney disease (‘CKD’) at any stage.

Optionally the ESWT treatment according to the present invention may beprovided to treat hypertension.

Most preferably the applied shockwaves are provided in a noninvasive,nondestructive manner, and do not cause tissue temperature elevationwhile utilizing low pressure amplitude, low energy shockwaves to bringabout the treatment to the kidney structures.

Most preferably the ESWT according to the present invention is providedunder the visual guidance of an imaging device for example including butnot limited to an ultrasound, CT, MRI or the like imaging technologyand/or devices as is known and practiced in the art.

Most preferably imaging device and/or technology provides for aiding indefining the ESWT focal zone where treatment is to be applied forexample including but not limited to the glomerulus 102, and/or adrenalgland 110, renal artery 50.

Optionally and preferably the shockwave treatment protocol may befocused on the glomerulus to bring about improved blood flowtherethrough and associated kidney structures. Optionally the treatmentaccording to the present invention may optionally further provide forremoving glomerular calci.

Optionally the ESWT treatment protocol according to the presentinvention may provide for the treatment of neural tissue and/or neuralfunction of tissue associated with the kidney and kidney structures viaoptional pathways for example including but not limited to regeneratingneural tissue and/or normalization of neural function and/ornormalization of neural activity and/or modification of neural functionand/or modification of neural activity and/or regulating neural activityand/or regulating neural functions and/or inhibiting neural activityand/or inhibiting neural function and/or promoting neural activityand/or promoting neural function, the like, or any combination thereof.

Optionally and preferably ESWT treatment according to the presentinvention provides for a cascade of molecular activity that brings aboutimproved renal blood flow through the glomerulus and/or other renalstructures and/or restored blood flow velocity in interlobular renalarteries.

Optionally a cascade of molecular activity may for example, involve butis not limited to at least one or more of the following regulatoryfactors selected from the group consisting of: vascular endothelialgrowth factor (VEGF), fibroblast growth factors (FGF), angiopoietins(Ang), platelet-derived growth factor, angiogenin, angiotropin,hepatocyte growth factor, platelet endothelial cell adhesion molecule,angiostatin, endostatin, thrombospondin, CXC chemokines, Nitric oxidesynthesis, NFkapaB activation, TNF-alpha mRNA expression, decreases theexpression of MCP1, decrease expression of CD3 mRNA, and pigmentepithelium.

Optionally the shockwave parameters utilized may be: a frequency ofabout 2 Hz and energy density from about 0.02 to about 0.18 mJ/mm².

Most preferably the shockwave parameters utilized are energy density ofabout 0.09 to about 0.1 mJ/mm²; at a frequency of about 2 Hz.

Optionally each treatment session may comprise up to about 5000shockwaves. Most preferably each treatment comprises about 2400shockwave that are delivered to the kidney structure. Optionally thenumber of shockwaves per treatment session may be applied to at leastone and more preferably a plurality of treatment zones 104 about thekidney structures. Optionally and more preferably a plurality of zonesfrom about 5 up to about 15 zones may be treated during a treatmentsession. Optionally each zone may be treated with about 100 shockwavesto about 500 shockwaves, that may distributed amongst a plurality ofzones from about 5 zones to about 15 zones forming the kidneystructures.

Optionally treatment may be provided at a particular structure or abouta plurality of structures within one treatment session.

Optionally treatment may be provided from different approaches to thekidney structures.

FIG. 2 shows a schematic non-limiting treatment protocol according tothe present invention where non-invasive ESWT treatment is provided to akidney structure where treatment is provided over a span of 9 weeks, asshown. The optional treatment protocol calls for 2 active treatmentsessions per week during weeks 1, 2, 3, 7, 8, and 9, while no treatmentis provided during weeks 4-6.

FIG. 3 shows a flowchart of an optional method of treatment of thekidney structures according to an optional embodiment of the presentinvention. First in stage 300 the kidney structure to be treated islocated with an imaging device, for example including but not limited toultrasound. Optionally and preferably the kidney structure to be treatedis identified from the prone approach. Next in stage 302, the shockwaveregimen is selected, treatment protocol adjusted and applied. Mostpreferably treatment protocol comprises 1800 shockwaves with shockwavefrequency of 2 Hz, and energy density of about 0.1 mJ/mm². Optionallyeither one or both kidneys are treated; optionally each kidney may betreated in turn, with shockwave regimen including 900 shockwaves withshockwave frequency of 2 Hz, and energy density of about 0.1 mJ/mm².

Optionally treatment of 2400 shockwaves is distributed amongst variouskidney structures forming a plurality of treatment zones, for examplefrom about 5 zones up to about 15 zones, therein providing from about100 to about 500 shockwaves per treatment zones.

Optionally the shock treatment may be applied to kidney structures froma plurality of optional approaches for example including but not limitedto prone (back), lateral (side), supine (stomach) any combinationthereof providing for appropriate non-invasive access to the kidneystructures to be treated. For example, an optional treatment protocolmay call for 900 shockwaves to be provided from the lateral position and900 from the prone position.

For example, an optional treatment protocol may for example call for1800 shockwaves delivered at a frequency of 2 Hz, with energy density ofabout 0.1 mJ/mm². Optionally the 2400 shockwaves may be distributedabout both kidneys amongst a plurality of treatment zones, from aplurality of zones for example:

100 shockwaves from the prone position targeting a kidney structureforming a single treatment zone of the left kidney, with frequency of 3Hz with energy density of 0.06 mJ/mm²;Next the right kidney is treated with 1650 shockwaves with frequency of2 Hz with energy density of 0.1 mJ/mm² distributed about a plurality oftreatment zones and kidney structures from a plurality of approaches(position) as follows;100 shockwaves from the prone position targeting a first kidneystructure forming a first treatment zone of the right kidney;next 650 shockwaves from the lateral position dispersed about aplurality of treatment zones comprising a second treatment zone providedwith 300 shockwaves, a third zones provided with about 100 shockwavesand a fourth treatment zone provided with about 250 shockwaves;next a further 900 shockwaves from the prone position delivered to aplurality of treatment zones, a fifth zone provided with 300 shockwavesand finally a sixth zone provides with 600 shockwaves.

Optionally and preferably treatment is repeated as necessary about atleast one or more focal zones 104.

Lastly, in stage 304 following treatment of all renal structures and/orzones a follow up period applied based on the structure treated.

While the invention has been described with respect to a limited numberof embodiments, it will be appreciated that many variations,modifications and other applications of the invention may be made.

What is claimed is:
 1. A method for restoring blood flow velocity in the interlobular renal arteries, the method comprising: applying an extracorporeal shockwave therapy (‘ESWT’) utilizing focused shockwaves generated with a shockwave generating system, applying between 1 and 2400 focused shockwaves having a repetition rate above one shockwave per second, and energy density of about 0.02 to 0.18 mJ/mm², to a plurality of renal structure treatment zones selected from: nephron, glomerulus, Bowman's capsule, tubules, medulla, renal artery, renal vein, renal pelvis, papilla, adrenal glands, adrenal cortex, adrenal medulla, phrenic arteries, and adrenal vein, neural tissue directly or indirectly innervating a kidney and renal structures, kidney neural system including renal sympathetic and renal para-sympathetic nerves, and renal sympathetic nerves that lie within and immediately adjacent to the wall of the renal arteries, or any combination thereof; wherein each of the plurality of treatment zones are provided with at least 100 shockwaves; and, wherein the shockwaves are delivered to the plurality of treatment zone during at least one session per week for up to about 20 sessions within a time frame of up to about 18 weeks.
 2. The method of claim 1, wherein the shockwaves are applied to from about 5 and up to about 15 treatment zones.
 3. The method of claim 1, wherein at least one of the plurality of renal structure treatment zones is the glomerulus so as to bring about a reduction of intra-glomerular hypertension.
 4. A method for improving renal function, the method comprising: applying an extracorporeal shockwave therapy (‘ESWT’) utilizing focused shockwaves generated with a shockwave generating system to at least one treatment zone of at least one renal structure selected from renal sympathetic and renal para-sympathetic nerves or renal sympathetic nerves that lie within and immediately adjacent to the wall of the renal arteries; the focused shockwave treatment protocol being applied at at least one session per week for up to 20 sessions within a period of up to about 18 weeks, the treatment protocol per session comprising delivery of at between 100 and 2400 shockwaves focused at the at least one treatment zone, the shockwaves having a repetition rate above 1 shockwave per second, and an energy density between 0.02 to 0.18 mJ/mm².
 5. The method of claim 4, wherein at least one of the shockwaves having a repetition rate between 2-4 shockwaves per second and an energy density of between 0.9-1.1 mJ/mm².
 6. The method of claim 4, wherein at least 1800 shockwaves are applied during one of the treatment sessions. 